Composition with a continuous aqueous phase containing L-2-oxothiazolidine-4-carboxylic acid

ABSTRACT

A composition containing a continuous aqueous phase comprising L-2-oxothiazolidine-4-carboxylic acid, at least one sequestering agent and at least one neutralizing agent, the said neutralizing agent being present in an amount which is sufficient to adjust the pH of the aqueous phase of the composition to a value of between 5 and 8. The combination of the sequestering agent and the neutralizing agent stabilizes the L-2-oxothiazolidine-4-carboxylic acid, in particular with respect to thermal degradation, and thus prevents yellowing of the composition and the formation of unpleasant odors.

CROSS REFERENCE TO RELATED APPLICATION

The present application is a Continuation of application Ser. No.09/522,106, filed Mar. 9, 2000 now U.S. Pat. No. 6,337,077.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to a composition with a continuous aqueousphase containing L-2-oxothiazolidine-4-carboxylic acid.

2. Background of the Invention

L-2-oxothiazolidine-4-carboxylic acid, or procysteine, is known as acomponent of cosmetic or dermatological compositions intended fortopical application to the skin. Such compositions can be intended forpreventing hair loss or for stimulating the regrowth of hair, asdescribed in EP 656 201. Procysteine is also known from patent FR 2 742658 as an agent for depigmenting or bleaching human skin.

However, procysteine has a certain level of instability, in particularwhen it is in the presence of water. Thus, when it is introduced into acosmetic composition, in particular a composition comprising water, itsefficacy decreases over time. In addition, after storage for a certainperiod, the composition into which it is introduced shows signs ofdegradation: coloration, odor, which users find unacceptable. Onesolution for stabilizing procysteine in water consists in combining itwith a polyol, in specific amounts by weight, and in limiting the amountof water to a value of 35% by weight, and preferably less than 20% byweight, relative to the total weight of the composition.

Although these compositions do in effect make it possible to conveyprocysteine stably over time without any loss of efficacy of this activeagent, not all users necessarily find their texture suitable and theneed remains for compositions capable of containing large amounts ofwater, for example greater than 80% by weight, in particular in the formof oil-in-water emulsions.

Admittedly, compositions in the form of oil-in-water emulsionscontaining procysteine are known from EP 656 201, but the Applicant hasobserved that these compositions were not stable over time and led to adegradation of the procysteine, resulting in the development of anauseating sulphureous odor and yellowing of the composition.

SUMMARY OF THE INVENTION

The Inventors have now found that the use, in combination, of asequestering agent and a neutralizing agent in an amount which issufficient to adjust the pH of the composition to a value of between 5and 8 makes it possible to formulate procysteine in compositions with acontinuous aqueous phase which remain stable over time and/or with thetemperature.

Accordingly, the present invention provides a composition, comprising:

-   -   a continuous aqueous phase comprising        L-2-oxothiazolidine-4-carboxylic acid, at least one sequestering        agent and at least one neutralizing agent, wherein the pH of the        aqueous phase is 5 to 8.

The composition obtained is stable, in particular with respect tothermal degradation, and also at water contents ranging up to 97% byweight, which makes it particularly suitable for cosmetic ordermatological applications.

The present invention also provides a method of preparing thecomposition described above by combining water,L-2-oxothiazolidine-4-carboxylic acid, the sequestering agent and anamount of at least one neutralizing agent effective to adjust the pH ofthe continuous aqueous phase to 5 to 8.

The present invention also provides a composition obtained by combiningwater, L-2-oxothiazolidine-4-carboxylic acid, at least one sequesteringagent and an amount of at least one neutralizing agent effective toadjust the pH of the composition to 5 to 8.

The present invention also provides a method of stabilizingL-2-oxothiazolidine-4-carboxylic acid in a composition containing acontinuous aqueous phase, comprising incorporating into the compositionat least one sequestering agent and at least one neutralizing agent,wherein the neutralizing agent being present in an amount which issufficient to adjust the pH of the aqueous phase of the composition to avalue of between 5 and 8.

The present invention also provides a method of depigmenting orbleaching the skin, body hairs and/or head hair, comprising applying theinventive composition to the skin, body hairs and/or head hair.

The present invention also provides a method of preventing hair lossand/or for stimulating regrowth of the hair, comprising applying theinventive composition to the hair.

The present invention also provides a method of preventing or treatinglight-induced ageing and/or environment-related stress of the skin,comprising applying the inventive composition to the skin.

The present invention also provides method of preventing or treatinggreasy skin, comprising applying the inventive composition to the skin.

A more complete appreciation of the invention and many of the attendantadvantages thereof will be readily obtained as the same becomes betterunderstood by reference to the following detailed description.

DETAILED DESCRIPTION OF THE INVENTION

Preferably, the composition according to the invention comprises from0.01 to 10% by weight, preferably from 0.1 to 5% and even morepreferably from 0.5 to 3% by weight, of L-2-oxothiazolidine-4-carboxylicacid relative to the total weight of the composition. These rangesinclude all specific values and subranges therebetween, such as 0.02,0.05, 0.2, 1, 2 and 8% by weight.

The terms “L-2-oxothiazolidine-4-carboxylic acid” or “procysteine” referto either the acid form or the carboxylate, since, as will be readilyappreciated by one skilled in the art, in an aqueous medium of pH 5 to 8there will be at least a portion of the carboxylate form of thecompound. As will be readily appreciated, the carboxylate will beion-paired with a cation, for example from the neutralizing agent.

The neutralizing agent used in the composition according to theinvention can be chosen in particular from: alkali metal hydroxides,such as sodium hydroxide and potassium hydroxide; ammonia; organic basessuch as monoethanolamine, diethanolamine, triethanolamine,aminomethyl-1,3-propanediol, N-methylglucamine and basic amino acidssuch as arginine and lysine; and mixtures thereof. The neutralizingagent is preferably triethanolamine.

The neutralizing agent is present in an amount which is sufficient toadjust the pH of the aqueous phase of the composition to between 5 and8, preferably between 6 and 7. To do this, a person skilled in the artcan readily adjust the amount of neutralizing agent as a function of theacids, other than the L-2-oxothiazolidine-4-carboxylic acid, which maybe present in the composition according to the invention and as afunction of the nature of the neutralizing agent. For example, when thecomposition according to the invention contains no acid other thanL-2-oxothiazolidine-4-carboxylic acid and when the neutralizing agentused is triethanolamine, the weight ratio of the neutralizing agent tothe L-2-oxothiazolidine-4-carboxylic acid is generally between 0.7:1 and1.3:1, better still between 0.9:1 and 1.2:1. According to one preferredembodiment of the invention, the weight ratio of the neutralizing agentto the L-2-oxothiazolidine-4-carboxylic acid is 1:1.

The sequestering agent combined with the neutralizing agent can bechosen in particular from: EDTA; EDTA salts such as the disodium andtetrasodium salts of EDTA or the dipotassium salt of EDTA; disodiumcocoamphodiacetate; diethylenetriamine pentaacetic acid and its salts,such as the pentasodium salt of diethylenetriamine pentaacetic acid; thetrisodium salt of nitrilotriacetic acid; ascorbic acid; trisodiumcitrate; etidronic acid and its salts, such as the tetrasodium salt ofetidronic acid; the heptasodium salt of diethylenetriaminepentamethylene phosphonic acid; the pentasodium salt ofdiethylenetriamine tetramethylene phosphonic acid; ethylenediaminetetramethylene phosphonic acid and its salts, such as the pentasodiumsalt of ethylenediamine tetramethylene phosphonic acid; sodiumglucoheptanoate; and mixtures thereof. Preferably, the sequesteringagent is an EDTA salt.

The sequestering agent is present, for example, in an amount of between0.01 and 1% by weight, preferably between 0.01 and 0.5% by weight, andbetter still in an amount of about 0.05% by weight, relative to thetotal weight of the composition. These ranges include all specificvalues and subranges therebetween, such as 0.02, 0.1, 0.2 and 0.8% byweight.

The composition according to the invention can be more or less fluid andcan have the appearance of a white or colored cream, a milk, a lotion, aserum, a mousse or an aqueous or aqueous-alcoholic gel. It can also bein the form of an aqueous or aqueous-alcoholic stick. The compositioncan optionally be applied to the skin or to the hair in the form of anaerosol.

According to one preferred embodiment, the composition according to theinvention is in the form of an emulsion of the oil-in-water type. Thisexpression generally means a mixture of two immiscible liquids, one ofwhich contains a discontinuous oily phase and the other of which forms acontinuous aqueous phase in which the oily phase is dispersed. As avariant, however, the oil-in-water emulsion can consist of a dispersionof oil in an aqueous phase using spherules, it being possible for thesespherules to be polymeric nanoparticles, such as nanospheres andnanocapsules, or lipid vesicles of ionic and/or nonionic type, such asthose described in patent applications EP 641 557 and EP 705 593, bothof which are incorporated herein by reference.

The composition according to the invention can be used as a care productand/or as a make-up product for the skin. It can also be in the form ofa shampoo or a conditioner.

In all cases, the composition comprises a physiologically acceptablemedium, i.e. a medium which is compatible with the skin or itssuperficial body growths.

When the composition is in the form of an oil-in-water emulsion, theproportion of the discontinuous fatty phase can represent from 0.5 to70% and preferably from 20 to 50% of the total weight of thecomposition. These ranges include all specific values and subrangestherebetween, such as 1, 2, 5, 10, 15, 25, 30, 40, 50 and 60% by weight.The oils, emulsifiers and co-emulsifiers used in the composition arechosen from those conventionally used in the field considered.

As oils which can be used in the invention, mention may be made ofmineral oils (liquid petroleum jelly), oils of plant origin (avocadooil, soybean oil), oils of animal origin (lanolin), synthetic oils(perhydrosqualene), silicone oils (cyclomethicone) and fluoro oils(perfluoropolyethers). Fatty substances which may also be used are fattyalcohols (cetyl alcohol), fatty acids or waxes (carnauba wax,ozokerite).

As emulsifiers and co-emulsifiers, it is possible to use any surfactantwhich produces an oil-in-water emulsion, and, for example: fatty acidesters of sorbitan, which are optionally polyoxyalkylenated, fatty acidesters of glycerol, fatty acid esters of a polyalkylene glycol, fattyalcohols, polyoxyethylenated fatty alkyl ethers, monoglyceryl ethersulphates, alkyl ether sulphates, alkyl or alkenyl oligoglycosides,N-alkylpolyhydroxyalkylamides of fatty acids, and mixtures thereof.

The emulsifier and the co-emulsifier are present in the composition in aproportion ranging from 0.3 to 30% by weight, and preferably from 0.5 to20% by weight, relative to the total weight of the composition. Theseranges include all specific values and subranges therebetween, such as1, 2, 5, 8, 10, 15 and 25% by weight. As a variant, the compositionaccording to the invention can be in the form of a surfactant-freeemulsion, containing a polymer such as the one available from EastmanChemical under the name AQ38S. This specific polymer is a polyestercontaining 89 mol % isophthalic acid, 11 mol % sodiosulphoisophthalicacid, 78 mol % diethylene glycol and 22 mol % 1,4-cyclohexane-methanol.

As will be readily appreciated by one skilled in the art, thecomposition according to the invention can also contain adjuvants whichare common in the cosmetics field, such as hydrophilic or lipophilicgelling agents, hydrophilic or lipophilic active agents, preservingagents, antioxidants, solvents, fragrances, fillers, screening agents,pigments, odor absorbers and dyestuffs. The amounts of these variousadjuvants are those used conventionally in the fields considered, and,for example, from 0.01 to 20% of the total weight of the composition.This range includes all specific values and subranges therebetween, suchas 0.02, 0.05, 1, 2, 5, 10 and 15% by weight. Depending on their nature,these adjuvants can be introduced into the fatty phase (when it ispresent), into the aqueous phase, into the lipid vesicles and/or intothe nanoparticles.

Hydrophilic gelling agents which may be mentioned in particular arecarboxyvinyl polymers (carbomer), acrylic copolymers such asacrylate/alkylacrylate copolymers, polyacrylamides, polysaccharides,natural gums and clays, and lipophilic gelling agents which may bementioned are modified clays such as bentones, metal salts of fattyacids and hydrophobic silica.

Active agents which can be used in particular are vitamins, keratolyticagents and/or desquamating agents such as 5-n-octanoylsalicylic acid, UVscreening agents, calmants and mixtures thereof. Other depigmentingagents can also be incorporated into the composition according to theinvention, such as kojic acid or hydroquinone and its derivatives,thereby allowing these agents to be used in lower doses. Agents forpreventing hair loss and/or for regrowth of the hair can also beincorporated into the composition according to the invention. In theevent of incompatibility, these active agents and/orL-2-oxothiazolidine-4-carboxylic acid can be incorporated intospherules, in particular ionic or nonionic vesicles and/or nanoparticles(nanocapsules and/or nanospheres), so as to isolate them from each otherin the composition. In addition, care will be taken to ensure that theactive agents which may be introduced into the composition according tothe invention, and their concentrations, do not modify the desiredproperties of the L-2-oxothiazolidine-4-carboxylic acid.

Preserving agents which may be used in particular are parabens andphenoxyethanol, but formaldehyde-donating preserving agents such asdiazolidinylurea are preferably avoided.

Another aspect of the invention is also the use of at least onesequestering agent combined with at least one neutralizing agent tostabilize L-2-oxothiazolidine-4-carboxylic acid in a composition with acontinuous aqueous phase, where the neutralizing agent is present in anamount which is sufficient to adjust the pH of the aqueous phase of thecomposition to a value of between 5 and 8.

Another aspect of the invention is a process for stabilizingL-2-oxothiazolidine-4-carboxylic acid in a composition with a continuousaqueous phase, by incorporating into the composition at least onesequestering agent and at least one neutralizing agent, when theneutralizing agent is present in an amount which is sufficient to adjustthe pH of the aqueous phase of the composition to a value of between 5and 8.

The composition according to the invention can be used, in the cosmeticsfield, in particular for the following purposes:

-   for depigmenting or bleaching the skin, body hairs and/or head hair;-   for preventing hair loss and/or for stimulating the regrowth of    hair;-   for preventing or treating light-induced ageing and/or    environment-related stress, in particular on account of the    radical-scavenging properties of L-2-oxothiazolidine-4-carboxylic    acid; and/or-   for preventing or treating greasy skin, for example in the treatment    of acne.

The term “environment-related stress” is defined as all of the chemicaland/or physical factors in degradation of the skin which are associatedwith urban life and, more specifically, with exposure of the skin tofine particles of pollutants floating in the air which are liable totrigger oxidation reactions on contact with the skin. These fineparticles may be contained, for example, in tobacco smoke, exhaust gasesor industrial flue gases. They may be in particular pollutants such asnitrogen oxides and active oxygen. The degradation of the state of theskin is reflected by one or more of the following symptoms: theformation of wrinkles, a reduction in the water content of the skin, theformation of squamae, a loss of radiance of the complexion, redness,etc.

Yet another aspect of the invention is also the use of the compositiondescribed above for the manufacture of a preparation intended forpreventing hair loss and/or for stimulating regrowth of the hair.

EXAMPLES

Having generally described this invention, a further understanding canbe obtained by reference to certain specific examples which are providedherein for purposes of illustration only and are not intended to belimiting unless otherwise specified. The percentages are given on aweight basis relative to the total weight of each constituent of thecomposition, unless stated otherwise.

Example 1

The composition below is prepared:

Cyclohexasiloxane 10% Apricot oil  6% Glycerol  5% Aluminium salt ofstarch crosslinked  3% with octenylsuccinic anhydride Stearyl alcoholand ceteareth-20  2% Methylglucose sesquistearate  2% Triethanolamine 1.1% L-2-Oxothiazolidine-4-carboxylic acid  1% Preserving agents  0.6%Xanthan gum  0.25% Disodium EDTA  0.05% Water 69%

The oil-in-water emulsion obtained has a pH of 6.6 and is stable for atleast 2 months at the following temperatures: 4° C., 25° C., 37° C. and45° C. No yellowing or production of odor by the composition areobserved at the end of this period. In addition, the level ofdegradation of the procysteine, as determined by HPLC, is less than 5%.

This composition can be applied to the skin in the morning and/orevening to fade away pigmentation marks.

Example 2 (Comparative)

An emulsion identical to that of Example 1 is prepared, except that itcontains no neutralizer (triethanolamine).

The emulsion obtained has a pH of 2.4. After two months, it gives off apronounced sulphureous odor at all the temperatures (4° C., 25° C., 37°C. and 45° C.). A 20% degradation of theL-2-oxothiazolidine-4-carboxylic acid is also observed for the emulsionstored for two months at 45° C.

Example 3 (Comparative)

An emulsion identical to that of Example 1 is prepared, except that itcontains no sequestering agent (disodium EDTA).

The emulsion has a pH of 6.6. After two months, it has a slight odor atall the temperatures (4° C., 25° C., 37° C. and 45° C.) and slightyellowing of the emulsions stored at 37° C. and 45° C. is also observed.

Example 4 (Comparative)

An emulsion identical to that of Example 1 is prepared, except that itcontains no neutralizing agent (triethanolamine) or sequestering agent(disodium EDTA).

The emulsion has a pH of 2.3. After two months, it has a pronouncedsulphureous odor and shows yellowing at all the temperatures (4° C., 25°C., 37° C. and 45° C.). A 14% degradation of theL-2-oxothiazolidine-4-carboxylic acid is also observed for the emulsionstored for two months at 45° C.

The above examples clearly illustrate the better stability of thecomposition according to the invention compared with compositionscomprising no sequestering agent and/or neutralizing agent.

Example 5

The composition below is prepared:

Phase A Stearyl alcohol  1% Mixture of glyceryl stearate and of  2%polyethylene glycol (100 EO) Cyclohexasiloxane 10% Phase B Glycerol  5%Sodium hydroxide  0.01% EDTA  0.05% Preserving agents  0.2% Water q.s.Phase C Xanthan gum  0.2% Water 20% Phase DL-2-Oxothiazolidine-4-carboxylic acid  1% Triethanolamine  1.1% Water20% Phase E Octenylsuccinate-modified starch  3% Silica  4%

Phase A and Phase B are heated separately to 80° C. and Phase A is thenintroduced into Phase B with stirring. After cooling, Phase C is thenadded to the emulsion obtained, followed by Phase D and finally Phase Eat about 40° C.

The emulsion obtained can be used to reduce the sheen of greasy skin.

Example 6

The composition below is prepared:

Phase A Mineral oil 10% Isopropyl myristate  2% Stearic acid  2.05%Stearyl alcohol and ceteareth-20  0.7% Glyceryl stearate  0.5% Phase BGlycerol  2% Preserving agents  0.2% Water q.s. Phase C Carbomer  0.1%Triethanolamine  0.1% Water 15% Phase D Alcohol 10% PhaseETriethanolamine  1.2% L-2-Oxothiazolidine-4-carboxylic acid  1.0% Water15%

Phases A and B are heated separately to 80° C. Phase A is then added toPhase B to obtain an oil-in-water emulsion, to which are successivelyadded Phases C, D and E.

An emulsion is obtained which is particularly suitable for protectingthe skin against the harmful effects of pollution.

Obviously, numerous modifications and variations of the presentinvention are possible in light of the above teachings. It is thereforeto be understood that within the scope of the appended claims, theinvention may be practiced otherwise than as specifically describedherein.

This application is based on French Patent Application Serial No.9903476, filed on Mar. 19, 1999, and incorporated herein by reference inits entirety.

1. A preventative method for protecting the skin from light-inducedageing and/or environment-related stress, comprising applying acomposition comprising: a continuous aqueous phase comprisingL-2-oxothiazolidine-4-carboxylic acid, at least one sequestering agent,and at least one neutralizing agent, to the skin, wherein the pH of theaqueous phase is 5 to
 8. 2. The method of claim 1, wherein thesequestering agent is selected from the group consisting of EDTA, EDTAsalts, disodium cocoamphodiacetate, diethylenetriamine pentaacetic acidand salts thereof, the trisodium salt of nitrilotriacetic acid, ascorbicacid, trisodium citrate, etidronic acid and salts thereof, theheptasodium salt of diethylenetriamine pentamethylene phosphonic acid,the pentasodium salt of diethylenetriamine tetramethylene phosphonicacid, ethylenediamine tetramethylene phosphonic acid and salts thereof,sodium glucoheptanoate, and mixtures thereof.
 3. The method of claim 1,wherein the sequestering agent is selected from the group consisting ofthe disodium and tetrasodium salts of EDTA, the dipotassium salt ofEDTA, the pentasodium salt of diethylenetriamine pentaacetic acid, thetetrasodium salt of etidronic acid, the pentasodium salt ofethylenediamine tetramethylene phosphonic acid, and mixtures thereof. 4.The method of claim 1, wherein the sequestering agent is an EDTA salt.5. The method of claim 1, wherein the neutralizing agent is selectedfrom the group consisting of sodium hydroxide, potassium hydroxide,ammonia, organic bases, basic amino acids, and mixtures thereof.
 6. Themethod of claim 1, wherein the neutralizing agent is selected from thegroup consisting of monoethanolamine, diethanolamine, triethanolamine,aminomethyl-1,3-propanediol, N-methylglucamine, arginine, lysine, andmixtures thereof.
 7. The method of claim 1, wherein the neutralizingagent is triethanolamine.
 8. The method of claim 1, wherein saidcomposition further comprises at least one other active agent selectedfrom the group consisting of vitamins, depigmenting agents, keratolyticagents and/or desquamating agents, calmants and UV screening agents. 9.The method of claim 1, wherein the composition further comprises atleast one oil and the composition is in the form of an oil-in-wateremulsion.
 10. The method of claim 1, wherein said composition comprises:0.01 to 10% by weight of L-2-oxothiazolidine-4-Carboxylic acid, 0.01 to1% by weight of the sequestering agent, wherein the weight ratio ofneutralizing agent to the L-2-oxothiazolidine-4-carboxylic acid is 0.7:1to 1.3:1.